The present invention relates to thiourea compounds useful as catalysts for asymmetric reactions. Moreover, the present invention pertains to methods of reacting a prochiral ketone catalyzed by a chiral thiourea catalyst in the presence of a borane.
Chirality continues to play an important role in the development of new pharmaceutical intermediates. Among the numerous techniques available today to industrial chemists, asymmetric synthesis has been used widely to obtain enantioenriched compounds. In many industrial processes, asymmetric catalysis is becoming the preferred approach because of its lower environmental impact and higher potential productivity. The asymmetric reduction of prochiral ketones to enantioenriched secondary alcohols is a prominent example of such a transformation in organic synthesis While an array of options is available, current demands for more economic and environmentally friendly protocols, especially metal free reagents, have introduced new challenges. One of the most widely applied, despite its sensitivity to air and moisture, of this new generation of catalytic asymmetric reducing systems is the Corey-Bakshi-Shibata (“CBS”) oxaborolidine.
In addition to their high costs and air and moisture sensitivity, B—H oxazaborolidines often contain impurities which diminish their effectiveness.